HoxB13 mediates AR-V7 activity in prostate cancer

Prostate cancer remains a leading cause of cancer death in the United States (1). In 2017, it was estimated that over 160,000 prostate cancer cases were diagnosed in the United States, and ∼26,000 men died of prostate cancer (2). Because tumor growth in prostate cancer is predominantly dependent on the androgen receptor (AR), a homodimer-forming transcription factor, the disease is commonly treated via therapies targeting the AR-axis. While this approach has proven to be initially effective, a majority of prostate cancer patients eventually develop resistance to AR-targeting therapies, leading to castration-resistant prostate cancer (CRPC), the lethal stage of prostate cancer. Measuring prostate-specific antigen levels in patient serum is regularly used for evaluating the efficacy of prostate cancer treatment. The serum prostate-specific antigen value, however, does not always correlate with the malignant state of CRPC (3). Therefore, it is of high priority to discover therapeutic targets and biomarkers that can accurately assess the efficacy of treatment in patients who have become resistant to therapies targeting the AR-axis.Various mechanisms of resistance to AR targeting have been identified, such as AR bypass signaling, AR alternative splicing, and AR gene amplification (4). Notably, aberrant AR splicing seems to be heavily associated with resistance to … [↵][1]1To whom correspondence should be addressed. Email: agoldstein{at}mednet.ucla.edu. [1]: #xref-corresp-1-1